1-236409068-TAAAAAA-TAAAAA

Variant names:

• chr1-236409068-TA-T
• rs772223735
• NM_145861.4:c.62-129delA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_145861.4(EDARADD):​c.62-129delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 202,838 control chromosomes in the GnomAD database, including 35 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0043 (1 hom., cov: 28)
  • Exomes 𝑓: 0.25 (35 hom.)
  • Failed GnomAD Quality Control
• Consequence: EDARADD NM_145861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

Genes affected

EDARADD (HGNC:14341): (EDAR associated via death domain) This gene was identified by its association with ectodermal dysplasia, a genetic disorder characterized by defective development of hair, teeth, and eccrine sweat glands. The protein encoded by this gene is a death domain-containing protein, and is found to interact with EDAR, a death domain receptor known to be required for the development of hair, teeth and other ectodermal derivatives. This protein and EDAR are coexpressed in epithelial cells during the formation of hair follicles and teeth. Through its interaction with EDAR, this protein acts as an adaptor, and links the receptor to downstream signaling pathways. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.62-129delA		intron_variant	Intron 1 of 5	ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.5	c.32-129delA		intron_variant	Intron 1 of 5		NP_542776.1
EDARADD	NM_001422628.1	c.-5-129delA		intron_variant	Intron 3 of 7		NP_001409557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9	c.62-147delA		intron_variant	Intron 1 of 5	1	NM_145861.4	ENSP00000335076.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 555 AN: 129096 Hom.: 1 Cov.: 28 FAILED QC

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00159

Gnomad EAS AF: 0.00227

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.00694

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.00906

GnomAD4 exome AF: 0.254 AC: 51474 AN: 202838 Hom.: 35 AF XY: 0.257 AC XY: 27336 AN XY: 106460

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00429 AC: 554 AN: 129094 Hom.: 1 Cov.: 28 AF XY: 0.00554 AC XY: 342 AN XY: 61774

Gnomad4 AFR AF: 0.00269

Gnomad4 AMR AF: 0.00374

Gnomad4 ASJ AF: 0.00159

Gnomad4 EAS AF: 0.00227

Gnomad4 SAS AF: 0.0248

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.00248

Gnomad4 OTH AF: 0.00902

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs772223735; hg19: chr1-236572368;